Hair is one of the defining characteristics of humans and mammals in general. With the exception of mucus membranes and glabrous skin, hair grows everywhere on a mammal's skin. Fine, short, light colored and barely noticeable ‘vellus hair’ growths initially during childhood, which is then gradually replaced by thick, long and colorful terminal hair from puberty onwards. The increase in androgenic hormone levels, particularly from the testosterone family, during puberty causes vellus hair to be replaced with terminal hair, as evidenced in the growth of terminal hair in the axillary, facial and pubic areas as well as on legs, arms and chest.
Changes in the levels of testosterone and testosterone derivatives drive both the change from vellus to terminal hair during puberty and, later in life, the more or less gradual onset of hair loss, which in either case naturally affect males more than females.
Hair growth begins inside the hair follicle, a minuscular, highly regenerative organ located in the dermis layer of mammalian skin that contains numerous mesenchymal stem cells for regrowing hair, once it has fallen out, as well as for regrowing skin, if it gets wounded. Each hair consists of a shaft, which is the hard filamentous part that extends above the skin or scalp surface, and a root or bulb that is embedded in the hair follicle. The human scalp contains in average about 100,000 to 150,000 hairs, with each hair having an average life span of several years.
The hair follicle perpetually undergoes cyclic transformations between phases of a) rapid growth where the hair shaft is produced and growths in length (anagen phase), b) a short transition stage that occurs at the end of the anagen phase (catagen phase) and c) a resting phase (telogen phase). It is the activity of the hair follicles that primarily determines hair growth and renewal (Krause & Foitzik, 2006). Typically, up to 90% of the hair follicles are in the anagen phase, about 1-2% in the catagen phase and about 8% in the telogen phase. For scalp hair, such a cycle takes several years to finish.
The final product of a hair follicle in the telogen stage is dead, fully keratinized hair (club hair); in average, 50-100 club hairs are daily shed from a regular scalp. Disturbances in the hair follicle cycling and hair morphogenesis can lead to unwanted hair loss or unwanted excessive hair growth with often profound impact on an individual's well-being far beyond the purely cosmetic aspect.
Alopecia, an androgen-mediated thinning of the scalp hair in men and women, is caused by a progressive shortening of the anagen growth cycle due to an oversensitivity to dihydrotestosterone. In men and women, a usually small percentage of testosterone undergoes reduction by the 5α-reductase to dihydrotestosterone. Depending on the genetic make-up of an individual, a higher percentage of testosterone can be converted to dihydrotestosterone, making the individual, thus, more prone to hair loss. An oversensitivity to dihydrotestosterone results in increased hair loss and by a gradual miniaturization and conversion of the hair follicles into vellus hair follicles which no longer produce thick, terminal hair, but hardly visible, depigmented hair. Loss of scalp hair starts usually at the temples and on the crown of the head and is more pronounced in men than in women. Alopecia can also be induced by chemical agents and is a frequently experienced adverse effect during anti-cancer chemotherapy. While alopecia is a serious disorder of hair growth and causes great psychological stress among the concerned, hair follicles are still present and are still cycling, which is critical, if reversal of hair loss is attempted.
Currently available treatments to address alopecia include the topical or oral application of pharmaceuticals, such as minoxidil (De Villez, 1985) or finasteride. Minoxidil, a vasodilating agent whose first indication is to lower arterial blood pressure, seems to only be effective at the start of androgenic alopecia and seems only to prevent hair loss, but does not seem to be able to effect new hair growth. Finasteride, a synthetic antiandrogen and specific inhibitor of type II 5α-reductase that transforms testosterone into dihydrotestosterone, has been shown to effectively decrease serum and scalp dihydrotestosterone (Leyden et al., 1999). However, since Finasteride is contraindicated in women and since it might also carry the risk for increased incidence of prostate cancer in men, its use is limited to men, carries risks and is not suited for long-term use.
Abnormally increased hair growth, as it is the case with hirsutism, an excessive androgen-dependent hair growth in women, and hypertrichosis, an excessive androgen-independent hair growth, results from an extended anagen phase with an unusual enlargement of hair follicles accompanied by the conversion of terminal to vellus hair follicles and consequential growth of terminal, thick hair instead of hardly visible, depigmented hair.
Cosmetic adjustment of hair growth is a further reason in today's society to modulate hair growth. Current methods for hair removal include shaving, electrolysis, depilatory creams and waxing, while the local application of herbal mixtures has been tried to encourage hair growth.
Far beyond posing a purely cosmetic problem, abnormal hair growth can seriously affect an individual's self-esteem and overall well-being. Currently available methods for modulating hair growth are not effective to achieve a measureable and sustainable improvement in hair growth. It would be highly desirable to have improved methods for modulating hair growth available that address the needs for reducing or increasing hair growth.